Unravelling the antitumoral potential of novel bis(thiosemicarbazonato) Zn(II) complexes: structural and cellular studies.

The development of pharmacologically active compounds based on bis(thiosemicarbazones) (BTSC) and on their coordination to metal centers constitutes a promising field of research. We have recently explored this class of ligands and their Cu(II) complexes for the design of cancer theranostics agents with enhanced uptake by tumoral cells. In the present work, we expand our focus to aliphatic and aromatic BTSC Zn(II) complexes bearing piperidine/morpholine pendant arms. The new complexes ZnL1-ZnL4 were characterized by a variety of analytical techniques, which included single-crystal X-ray crystallography for ZnL2 and ZnL3. Taking advantage of the fluorescent properties of the aromatic complexes, we investigated their cellular uptake kinetics and subcellular localization. Furthermore, we tried to elucidate the mechanism of action of the cytotoxic effect observed in human cancer cell line models. The results show that the aliphatic complexes (ZnL1 and ZnL2) have a symmetrical structure, while the aromatic counterparts (ZnL3 and ZnL4) have an asymmetrical nature. The cytotoxic activity was higher for the aromatic BTSC complexes, as well as the cellular uptake, evaluated by measurement of intracellular Zn accumulation. Among the most active complexes, ZnL3 presented the fastest uptake kinetics and lysosomal localization assessed by live-cell microscopy. Detailed studies of its impact on cellular production of reactive oxygen species and impairment of lysosomal membrane integrity reinforced the influence of the pendant piperidine in the biological performance of aromatic BTSC Zn(II) complexes.

Profiles of paralytic shellfish poisoning toxins in shellfish from Portugal explained by carbamoylase activity.

The presence of paralytic shellfish poisoning (PSP) toxins has not been recorded in the Portuguese coast since 1995. A bloom of Gymnodinium catenatum occurred in the NW coast of Portugal in the autumn of 2005, and PSP profiles were determined in several inshore and offshore shellfish species by HPLC after pre-column oxidation. Most of the species studied contained a complex toxin profile, typically representative of contamination by G. catenatum. However, clams such as Spisula solida contained mainly decarbamoyl toxins, while less extensive transformation was found in Scrobicularia plana. In vitro incubation of S. solida digestive glands with PSP standards revealed a rapid transformation of carbamate and N-sulfocarbamoyl toxins into their corresponding decarbamate analogues. After 24 h, less than 5% of the carbamate or N-sulfocarbamoyl toxins tested remained. After a 24 h in vitro incubation of S. plana digestive glands, no decarbamate analogues were detected. Artificial toxification of S. plana with cultures of G. catenatum revealed the conversion into decarbamoyl analogues progressed slowly: initially dcGTX2+3 and dcSTX accounted only for 5% of total non N-1 hydroxilated toxins, after 6 days these toxins accounted for 41% of the toxin composition. In vitro incubations of digestive glands from other commercial bivalves did not reveal production of decarbamoyl analogues over a 24 h period.